@Article{096504020X15929939001042,
AUTHOR = {Yanhui Li, Su Dong, Arya Tamaskar, Heather Wang, Jing Zhao, Haichun Ma, Yutong Zhao},
TITLE = {Proteasome Inhibitors Diminish c-Met Expression and Induce Cell Death  in Non-Small Cell Lung Cancer Cells},
JOURNAL = {Oncology Research},
VOLUME = {28},
YEAR = {2020},
NUMBER = {5},
PAGES = {497--507},
URL = {http://www.techscience.com/or/v28n5/48509},
ISSN = {1555-3906},
ABSTRACT = {Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and accounts for 85% of all 
lung carcinomas. The hepatocyte growth factor receptor (c-Met) has been considered as a potential therapeutic target for NSCLC. Proteasome inhibition induces cell apoptosis and has been used as a novel therapeutic 
approach for treating diseases including NSCLC; however, the effects of different proteasome inhibitors on 
NSCLC have not been fully investigated. The aim of this study is to determine a precise strategy for treating 
NSCLC by targeting c-Met using different proteasome inhibitors. Three proteasome inhibitors, bortezomib, 
MG132, and ONX 0914, were used in this study. Bortezomib (50 nM) significantly reduced c-Met levels and 
cell viability in H1299 and H441 cells, while similar effects were observed in H460 and A549 cells when a 
higher concentration (~100 nM) was used. Bortezomib decreased c-Met gene expression in H1299 and H441 
cells, but it had no effect in A549 and H460 cells. MG-132 at a low concentration (0.5 µM) diminished c-Met 
levels in H441 cells, while neither a low nor a high concentration (~20 µM) altered c-Met levels in A549 and 
H460 cells. A higher concentration of MG-132 (5 µM) was required for decreasing c-Met levels in H1299 
cells. Furthermore, MG-132 induced cell death in all four cell types. Among all the four cell lines, H441 cells 
expressed higher levels of c-Met and appeared to be the most susceptible to MG-132. MG-132 decreased c-Met 
mRNA levels in both H1299 and H441 cells. ONX 0914 reduced c-Met levels in H460, H1299, and H441 cells 
but not in A549 cells. c-Met levels were decreased the most in H441 cells treated with ONX 0914. ONX 0914 
did not alter cell viability in H441; however, it did induce cell death among H460, A549, and H1299 cells. This 
study reveals that different proteasome inhibitors produce varied inhibitory effects in NSCLS cell lines.},
DOI = {10.3727/096504020X15929939001042}
}